Benefits of Tiotropium/Olodaterol Compared with Tiotropium in Patients with COPD Receiving only LAMA at Baseline: Pooled Analysis of the TONADO ® and OTEMTO ® Studies

Adv Ther. 2020 Aug;37(8):3485-3499. doi: 10.1007/s12325-020-01373-3. Epub 2020 May 27.

Abstract

Introduction: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report recommends long-acting muscarinic antagonists (LAMA) or long-acting β2-agonists (LABA) as first-line treatment for chronic obstructive pulmonary disease (COPD), but many patients remain symptomatic on monotherapy and escalation to dual-bronchodilator therapy may be warranted.

Methods: TONADO® 1&2 and OTEMTO® 1&2 assessed lung function and patient-reported outcomes in patients with moderate-to-severe (OTEMTO) or moderate-to-very-severe (TONADO) COPD. This pooled post hoc analysis included patients treated with LAMA monotherapy at baseline who were randomised to receive either 5 µg tiotropium (LAMA) or 5/5 µg tiotropium/olodaterol (LAMA/LABA). We assessed changes from baseline and responder rates for trough forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) and the Transition Dyspnoea Index (TDI).

Results: Overall, 151 patients received tiotropium; 148 received tiotropium/olodaterol. Mean differences from baseline with tiotropium/olodaterol versus tiotropium were + 0.074 l (95% confidence interval [CI] 0.033, 0.115; P = 0.0004) for trough FEV1, - 2.675 (95% CI - 5.060, - 0.291; P = 0.0280) for SGRQ and 1.148 (95% CI 0.564, 1.732; P = 0.0001) for TDI. Patients were more likely to respond when treated with tiotropium/olodaterol versus tiotropium for trough FEV1 (odds ratio [OR] 3.14, 95% CI 1.94, 5.06; P < 0.0001), SGRQ (OR 1.49, 95% CI 0.93, 2.40; P = 0.0980) and TDI (OR 2.81, 95% CI 1.71, 4.60; P < 0.0001). Minimum clinically important difference from baseline in any of the analysed outcomes (FEV1 ≥ 0.1 l, SGRQ ≥ 4.0 points or TDI ≥ 1.0 point) was more likely in patients treated with tiotropium/olodaterol versus tiotropium (OR 2.43, 95% CI 1.32, 4.51; P = 0.0046).

Conclusion: In patients with COPD receiving only LAMA monotherapy, treatment escalation to tiotropium/olodaterol resulted in statistically significant and clinically relevant improvements in lung function, health status and breathlessness. These results support early therapy optimisation to dual bronchodilation with tiotropium/olodaterol in patients receiving tiotropium alone.

Trial registration: TONADO® 1 was registered in the US National Library of Medicine on 9 September 2011 (Clinicaltrials.gov: NCT01431274). TONADO® 2 was registered in the US National Library of Medicine on 9 September 2011 (Clinicaltrials.gov: NCT01431287). OTEMTO® 1 was registered in the US National Library of Medicine on 17 October 2013 (Clinicaltrials.gov: NCT01964352). OTEMTO® 2 was registered in the US National Library of Medicine on 10 December 2013 (Clinicaltrials.gov: NCT02006732).

Keywords: Bronchodilator; FEV1; LAMA; OTEMTO; SGRQ; TDI; TONADO; Tiotropium/olodaterol.

Plain Language Summary

Global recommendations suggest that people with chronic obstructive pulmonary disease (COPD) can start treatment with one of two types of inhaled medicine: either a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA). Doctors can also prescribe these treatments together (LAMA/LABA) if needed. To help doctors decide whether to prescribe single or combined treatment, we looked at people with COPD who were taking LAMA alone at the beginning of two large studies (TONADO® and OTEMTO®). In these studies, people with COPD could either stay on LAMA alone (tiotropium) or switch to combined LAMA/LABA treatment (tiotropium/olodaterol). We looked to see if there were any changes in the functioning of the lungs (measured using forced expiratory volume in 1 s), quality of life (measured using the St. George’s Respiratory Questionnaire) or breathlessness (measured using the Transition Dyspnoea Index) between the start of the study and after 12 weeks of treatment. We showed that lung function, health-related quality of life and breathlessness were significantly better in people taking tiotropium/olodaterol for 12 weeks compared with those on tiotropium alone. Overall, our results support global recommendations and suggest that many people with COPD who are treated with tiotropium could benefit from stepping up to tiotropium/olodaterol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzoxazines / therapeutic use*
  • Bronchodilator Agents / therapeutic use*
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Respiratory Function Tests
  • Tiotropium Bromide / therapeutic use*

Substances

  • Benzoxazines
  • Bronchodilator Agents
  • Drug Combinations
  • olodaterol
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01431287
  • ClinicalTrials.gov/NCT01431274
  • ClinicalTrials.gov/NCT01964352
  • ClinicalTrials.gov/NCT02006732